Matrix-assisted ionization methods such as matrix-assisted laser desorption ionization have proven useful in spectroscopic analysis of organic and biologic compounds. In the MALDI technique, a sample is combined with an organic matrix that co-crystallizes with the sample, and then deposited on a sample plate. The sample plate may contain a large number of such samples, with each sample occupying a small area on the surface of the plate. The sample plate is placed in a MALDI ion source, where a laser beam directed at the sample vaporizes the matrix, and ionizes the analyte compounds within the sample.
In a MALDI system, a laser beam is focused at a specific target area on the sample plate containing a particular sample of interest. An imaging device is setup to visualize the target area and the trajectory of the laser beam, to locate the sample of interest and ensure it is in the target area, to confirm that the laser beam is aligned correctly for impacting the sample in the target area and also to view the interaction of the laser beam with the sample matrix.
In conventional MALDI sources, the laser beam that is used to vaporize the sample and the optical radiation (usually visible light radiation) which reflects off of the sample and is captured by the imaging device, follow separate optical paths. In particular, the laser beam, which may comprise ultraviolet radiation, is usually directed along a dedicated optical path separate from other optical paths. Because of the separation between these optical paths, misalignment errors, in which the area on the sample plate surface viewed using the imaging device does not match the target area impacted by the laser beam, can be difficult to avoid, with the result that it is difficult to determine whether the laser beam is directed at the sample of interest in the target area.
Moreover, employment of optical devices that can enhance the resolution of such systems by allowing the viewing and the ionization of smaller target areas and samples, such as powerful optical lenses that provide focusing and magnification, is especially problematic in MALDI systems in which the laser and visible optical paths are separate, since the employment of such devices in either optical path (or both) can exacerbate the misalignment of the paths, or require expensive and duplicative mechanisms for readjustment of the paths. Since increased optical resolution can enhance the throughput and efficiency of MALDI sources, there is a need for a MALDI system and method in which such misalignment problems are not likely to occur, or are likely occur to a much more limited extent, enabling the employment of optical devices that facilitate improved sample utilization and throughput.